SPID#: 6 The objective of this study is to better understand the generalmechanisms that lead to the regulation of specific B cell and antibody responses involved either in protective mechanisms against infectious diseases or in deleterious events that may lead to the breakdown of the immune system. To accomplish this objective, we are evaluating 1) the antibody responses generated following viral infection in macaques or experimental injection of selected antigens in mice and 2) the natural autoantibody patterns present in mice and macaques as well as the normal background recognition of non-organ specific autoantigens in macaques. HIV infection in humans and SIV infection in macaques are classical examples in which immune responses specific for the corresponding pathogen are accompanied by B cell dysfunctions and production of autoantibodies. Therefore, we are examining these dysfunctions in SIV-infected rhesus monkeys. Results from this study should help in understanding whether or not such dysfunctions are involved in the pathogenesis of AIDS and in designing strategies for their control. Antibody responses can be regulated, quantitatively and qualitatively, using different immunization methods. For this reason, we are evaluating the influence that DNA immunization exerts on the development of antibodies specific for the CD4 molecule, a major HIV and SIV cellular receptor. Our results show that, in mice, DNA immunization leads to recognition of more conformational epitopes and involvement of different subsets of T helper cells as compared to immunization with soluble CD4. These studies will provide useful information on how to manipulate the antibody production in order to induce protective immunity and avoid deleterious responses.